Interactions of cardiac glycosides with cultured cardiac cells: II. Biochemical and electron microscopic studies on the effects of ouabain on muscle and non-muscle cells |
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Authors: | Ishayahu Friedman Herzl Schwalb Haifa Hallaq Arie Pinson Michael Heller |
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Affiliation: | 1. Department of Pathology, Department of Biochemistry, The Hebrew University, Hadassah Medical School, Jerusalem Israel;2. Myocardial Research Group, Department of Biochemistry, The Hebrew University, Hadassah Medical School, Jerusalem Israel |
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Abstract: | Electron microscopic and biochemical studies revealed a salient difference in the response to toxic doses of ouabain by cultured cardiac muscle and non-muscle cells from neonatal rats. Progressive cellular injury in myocytes incubated with 1 · 10?4–1 · 10?3 M ouabain ultimately leads to swelling and necrosis. The morphological damage in myocytes was accompanied by a drastic decrease in 14CO2 formation from 14C-labeled stearate or acetate but not glucose. Neither morphological nor biochemical impairments were observed in non-muscle cells. The interaction between ouabain and the cultured cells, using therapeutic doses of ouabain (i.e., <1 · 10?7 M), was characterized. Two binding sites were described in both classes of cells, one site is a saturable K+-sensitive site whereas the other is non-saturable and K+-insensitive. The complexes formed between the sarcolemma receptor(s) and ouabain, at low concentrations of the drug (e.g., 7.52 · 10?9 M), had Kd values of 8.9 · 10?8 and 2.3 · 10?8 M for muscle and non-muscle cells, respectively. The formation and dissociation of the complexes were affected by temperature and potassium ions. |
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Keywords: | Cardiac cell Ouabain Toxicity Binding site Cardiac glycoside CDC critical digitalis concentration |
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